(Circulation. 1997;96:1398-1402.)
© 1997 American Heart Association, Inc.
Articles |
Simvastatin Reduces Graft Vessel Disease and Mortality After Heart Transplantation
A Four-Year Randomized Trial
From the Department of Cardiac Surgery (K.W.), Munich- Bogenhausen; Department of Cardiac Surgery (B.M., B.R.), University Hospital, Munich-Grosshadern; Institute of Clinical Chemistry (J.T., D.N., D.S.), Medical Statistics, University Hospital, Munich-Grosshadern; and Department of Medicine I (W. von S., G.S.), University Hospital, Munich-Grosshadern, Germany.
Correspondence to Dr K. Wenke, Department of Cardiac Surgery, Munich-Bogenhausen, D-81925 Munich, Germany.
Background Accelerated graft vessel disease (GVD) represents the most serious long-term complication of heart transplantation. A possible cause underlying this progressive coronary vascular disease is believed to be post-transplantation hypercholesterolemia.
Methods and Results In a 4-year prospective randomized study with heart transplant recipients, the efficacy of primary antihypercholesterolemic therapy with simvastatin was compared with that of general dietary therapy. The aim of the treatment was to maintain post-transplantation LDL-cholesterol levels at <120 mg/dL. Seventy-two heart transplant recipients receiving standard triple immunosuppression were randomly assigned to an active-treatment group (low-cholesterol diet and simvastatin, n=35) or a control group (general dietary measures, n=37). In the course of 4 years after transplantation, the simvastatin group had significantly lower LDL-cholesterol concentrations than the control group (mean±SD, 115±14 versus 156±17 mg/dL, P=.002), a significantly better long-term survival (88.6% versus 70.3%, P=.05), and a lower incidence of GVD in the coronary angiographic findings (16.6% versus 42.3%, P=.045). The incidence of graft rejections did not differ between the two groups, although there was a tendency toward a lower number of serious rejections in the simvastatin group (2.8% versus 13.5%, P=.1). Intracoronary ultrasound performed after 4 years in a subgroup of 27 patients (simvastatin, 10; control, 17) showed less intimal thickening in patients with LDL-cholesterol levels of <110 mg/dL (170±84 versus 370±171 µm, P=.04) and a lower intimal index (13.8±7.1% versus 27.9±12.1%, P=.04).
Conclusions In comparison with dietary measures alone, the combination of a low-cholesterol diet and simvastatin after heart transplantation led to a significant reduction in cholesterol levels, a significantly higher long-term survival rate, and a lower incidence of GVD.
Key Words: simvastatin • hypercholesterolemia • transplantation • graft vessel disease
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